Douthwaite S, Champney W S
Department of Biochemistry and Molecular Biology, Odense University, DK-5230 Odense M, Denmark.
J Antimicrob Chemother. 2001 Sep;48 Suppl T1:1-8. doi: 10.1093/jac/48.suppl_2.1.
Ketolides are the most recent generation of antimicrobials derived from the 14-membered ring macrolide, erythromycin A. The main structural feature that differentiates ketolides from erythromycin is the keto group, which replaces the L-cladinose moiety at position 3 of the macrolactone ring. The keto group bestows greater acid stability on the drugs, and enables them to bind to their ribosomal target without causing expression of MLS(B) resistance in inducible strains. Several ketolides are described here, including ABT 773 and telithromycin (HMR 3647), both of which possess a carbamate at C11/C12 of the macrolactone ring. In telithromycin, which is the first ketolide to be approved for clinical use, the carbamate is linked to an alkyl-aryl extension, which is responsible for the increased potency of this compound relative to macrolides. This review examines how the structural differences between macrolides and the new ketolides are related to their antimicrobial activities in inhibiting protein synthesis and blocking the assembly of new ribosomal subunits.
酮内酯类是源自14元环大环内酯类药物红霉素A的最新一代抗菌药物。酮内酯类与红霉素的主要结构特征区别在于酮基，它取代了大环内酯环3位上的L-克拉定糖部分。酮基赋予药物更高的酸稳定性，并使其能够与核糖体靶点结合，而不会在诱导型菌株中引发MLS(B)耐药性的表达。本文介绍了几种酮内酯类药物，包括ABT 773和泰利霉素（HMR 3647），两者在大环内酯环的C11/C12位均含有一个氨基甲酸酯。在首个被批准用于临床的酮内酯类药物泰利霉素中，氨基甲酸酯与一个烷基芳基延伸部分相连，这使得该化合物相对于大环内酯类药物的效力增强。本综述探讨了大环内酯类药物与新型酮内酯类药物之间的结构差异如何与其在抑制蛋白质合成和阻止新核糖体亚基组装方面的抗菌活性相关。
